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Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation


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Chan, YJ, Liao, PL, Tsai, CH, Cheng, YW, Lin, FL, Ho, JD, Chen, CY and Li, CH 2021 , 'Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation' , Particle and Fibre Toxicology, vol. 18, no. 1 , pp. 1-16 , doi: 10.1186/s12989-020-00395-7.

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Background:Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufacturedextensively and widely present in our daily necessities, with growing environmental release and public concerns. Insunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPsmay occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understandthe barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinalendothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction componentsand functions.Results: TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreasedtransendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This mightinvolve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NPintravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reducedblood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciablechange in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in theTiO2-NP-treated eyes.Conclusions: Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affectingretinal electrophysiology.

Item Type: Article
Authors/Creators:Chan, YJ and Liao, PL and Tsai, CH and Cheng, YW and Lin, FL and Ho, JD and Chen, CY and Li, CH
Keywords: titanium dioxide nanoparticles, endothelial cells, claudin-5, ADAM17, blood-retinal barrier
Journal or Publication Title: Particle and Fibre Toxicology
Publisher: BioMed Central Ltd.
ISSN: 1743-8977
DOI / ID Number: 10.1186/s12989-020-00395-7
Copyright Information:

Copyright 2021 the Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

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